HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T Cell Lymphoma.

Peripheral T cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Here, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing MNU-induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL. Key words: Histone deacetylases (HDACs), Natural killer (NK) cells, Peripheral T cell lymphoma (PTCL).

The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer.

OBJECTIVE: To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. METHODS: One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. RESULTS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995-16.330, p < 0.001). CONCLUSIONS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.

Post-transplant cyclophosphamide at 80 mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning.

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients.

Nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf, South China Sea: Implication for the severe impact of human disturbance.

This study examined the nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf (CNBG). Nutrient concentrations varied spatially and seasonally among the different bays. High nutrient levels were found in the regions with high riverine inputs and intensive mariculture. Using a three end-member mixing model, nutrient biogeochemistry within the ecosystem was estimated separately from complex physical mixing effects. Nutrient consumption dominated in most bays in summer, whereas nutrient regeneration dominated in winter, likely due to phytoplankton decomposition, vertical mixing and desorption. Through the Land-Ocean Interaction Coastal Zone (LOICZ) model, the robust nutrient budgets were constructed, indicating that the CNBG behaved as a sink of dissolved inorganic nitrogen, phosphorus and silicon. River-borne nutrient inputs were the dominant nutrient source, while residual flows and water exchange flows transported nutrient off the estuaries. This study could help us better understand nutrient cycles and nutrient sources/sinks in the CNBG.

Sculpting Mesoscopic Helical Chirality into Covalent Organic Framework Nanotubes from Entirely Achiral Building Blocks.

The diversification of chirality in covalent organic frameworks (COFs) holds immense promise for expanding their properties and functionality. Herein, we introduce an innovative approach for imparting helical chirality to COFs and fabricating a family of chiral COF nanotubes with mesoscopic helicity from entirely achiral building blocks for the first time. We present an effective 2,3-diaminopyridine-mediated supramolecular templating method, which facilitates the prefabrication of helical imine-linked polymer nanotubes using unprecedented achiral symmetric monomers. Through meticulous optimization of crystallization conditions, these helical polymer nanotubes are adeptly converted into imine-linked COF nanotubes boasting impressive surface areas, while well preserving their helical morphology and chiroptical properties. Furthermore, these helical imine-linked polymers or COFs could be subtly transformed into corresponding more stable and functional helical ß-ketoenamine-linked and hydrazone-linked COF nanotubes with transferred circular dichroism via monomer exchange. Notably, despite the involvement of covalent bonding breakage and reorganization, these exchange processes overcome thermodynamic disadvantages, allowing mesoscopic helical chirality to be perfectly preserved. This research highlights the potential of mesoscopic helicity in conferring COFs with favourable chiral properties, providing novel insights into the development of multifunctional COFs in the field of chiral materials chemistry.

Linked color imaging-based endoscopic grading of gastric intestinal metaplasia and histological gastritis staging in the assessment of gastric cancer risk.

OBJECTIVE: To evaluate the value and compare the effectiveness of linked color imaging-based endoscopic grading of gastric intestinal metaplasia (LCI-EGGIM) and operative link on gastric intestinal metaplasia (OLGIM) in risk stratification of early gastric cancer (EGC). METHODS: Eighty-one patients with EGC who underwent endoscopic submucosal dissection were included. The general data and EGC-related risk factors of all participants were recorded. LCI-EGGIM and OLGIM were used for both groups. RESULTS: The number of patients with LCI-EGGIM score ≥ 5 was significantly higher in the EGC group than in the control group (58.02% vs. 12.35%, p < .001). Furthermore, the number of patients with OLGIM stage III/IV in the EGC group was significantly higher than that in the control group (56.79% vs. 7.41%, p < .001). Multivariate analysis showed that OLGIM stage III/IV (adjusted odds ratio [AOR]: 29.74, 95% CI: 7.49-117.94) and LCI-EGGIM score ≥ 5 (AOR: 12.33, 95% CI: 3.71-41.02) were significantly associated with EGC. There was no significant difference in the area under the receiver operating characteristic curve between LCI-EGGIM and OLGIM in predicting the risk of EGC (0.74 vs. 0.77, p = .1116). CONCLUSION: OLGIM and LCI-EGGIM can be used and have the same value for predicting the risk stratification of EGC in patients with gastric intestinal metaplasia.

A Rapid Detection Method for Fungal Spores from Greenhouse Crops Based on CMOS Image Sensors and Diffraction Fingerprint Feature Processing.

The detection and control of fungal spores in greenhouse crops are important for stabilizing and increasing crop yield. At present, the detection of fungal spores mainly adopts the method of combining portable volumetric spore traps and microscope image processing. This method is problematic as it is limited by the small field of view of the microscope and has low efficiency. This study proposes a rapid detection method for fungal spores from greenhouse crops based on CMOS image sensors and diffraction fingerprint feature processing. We built a diffraction fingerprint image acquisition system for fungal spores of greenhouse crops and collected diffraction fingerprint images of three kinds of fungal spores. A total of 13 diffraction fingerprint features were selected for the classification of fungal spores. These 13 characteristic values were divided into 3 categories, main bright fringe, main dark fringe, and center fringe. Then, these three features were calculated to obtain the Peak to Center ratio (PCR), Valley to Center ratio, and Peak to Valley ratio (PVR). Based on these features, logistics regression (LR), K nearest neighbor (KNN), random forest (RF), and support vector machine (SVM) classification models were built. The test results show that the SVM model has a better overall classification performance than the LR, KNN, and RF models. The average accuracy rate of the recognition of three kinds of fungal spores from greenhouse crops under the SVM model was 92.72%, while the accuracy rates of the LR, KNN, and RF models were 84.97%, 87.44%, and 88.72%, respectively. The F1-Score value of the SVM model was higher, and the overall average value reached 89.41%, which was 11.12%, 7.18%, and 5.57% higher than the LR, KNN, and RF models, respectively. Therefore, the method proposed in this study can be used for the remote identification of three fungal spores which can provide a reference for the identification of fungal spores in greenhouse crops and has the advantages of low cost and portability.

The role of school organizational conditions in teacher psychological resilience and stress during COVID-19 pandemic: A moderated mediation model.

Educational revisions facilitate the relief of teacher stress by means of enhancing school organizational conditions. However, limited research has explored the effects of school organizational conditions on teacher stress in China. Using a sample of 734 primary and secondary school teachers from 30 provinces or municipalities of China, this study examined the effects of school organizational conditions on teacher stress in China, with a particular focus on the mediating role of psychological resilience and moderating role of perceived COVID-19 crisis strength. The results demonstrated that school organizational conditions were negatively associated with teacher stress. Furthermore, psychological resilience partially mediated the relation between school organizational conditions and teacher stress. In addition, perceived COVID-19 crisis strength significantly moderated the direct and indirect relations between school organizational conditions and teacher stress. The relations between school organizational conditions and teacher stress and between school organizational conditions and psychological resilience were stronger for teachers who perceived low levels of COVID-19 crisis strength. However, the indirect relation between psychological resilience and stress was stronger for teachers who perceived high levels of COVID-19 crisis strength. Implications have been provided accordingly.

Handedness Inversion of Chiral 3-Aminophenol Formaldehyde Resin Nanotubes Mediated by Metal Coordination.

Precise adjustment of microstructure and handedness of chiral nanomaterials is important to regulate their properties and performance. Herein, helical 3-aminophenol formaldehyde resin (APF) nanotubes and corresponding carbonaceous nanotubes with controllable handedness and optical activity were obtained via an external metal ion-mediated supramolecular co-templating method in an enantiomerically pure template system, in which an appropriate amount of Mn2+ (Co2+ or Ni2+ ) with moderate coordination abilities can reverse the spatial arrangement of the phenylglycine-based amphiphilic template molecules through metal coordination. Different stacking modes of coordination complexes in disparate metal ion systems lead to diverse helical senses (diameter and pitch) of the obtained helical APF. In addition, this coordination mode of metal intervention can be applied to other amine-based helical polymer synthesis systems, which paves the way for the design of high-quality chiral nanomaterials with satisfactory physical parameters and properties.

Imprinted propyl gallate electrochemical sensor based on graphene/single walled carbon nanotubes/sol-gel film.

A novel imprinted sol-gel electrochemical sensor for the determination of propyl gallate (PG) was developed based on a composite of graphene and single walled carbon nanotubes (GR-SWCNTs). It was fabricated by stepwise modifying GR-SWCNTs and molecularly imprinted polymers and stored in 0.10 mol L(-1) phosphate buffer solution pH 6.0, which endowed the sensor good sensitivity and selective recognition towards template molecules. The morphology and specific adsorption capacity of the sensor was characterized by scanning electron microscope and electrochemical methods, respectively. Under the optimized conditions, a linear range of the sensor to PG was 8.0 × 10(-8)-2.6 × 10(-3)mo lL(-1) with a limit of detection of 5.0 × 10(-8)mol L(-1) (S/N=3). The sensor exhibited specificity and selectivity towards template molecules as well as excellent reproducibility, regeneration and stability. Furthermore, the sensor could be applied to determine PG in edible oils, instant noodles and cookies with satisfactory results.

Transarterial chemoembolization with/without cryotherapy is associated with improved clinical outcomes of sorafenib for the treatment of advanced hepatocellular carcinoma.

Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma (HCC), but with limited efficacy. The present study aimed to prospectively investigate the efficacy and analyze the prognostic factors for survival in sorafenib-treated patients with advanced HCC. The baseline characteristics and clinical outcomes of 110 patients with advanced hepatitis B virus-related HCC treated with sorafenib with/without local therapy (transarterial chemoembolization with/without cryoablation) at a single liver cancer center were recorded. Predictors of progression-free survival (PFS) and overall survival (OS) were determined by multivariate analysis. A total of 14 (12.7%) patients achieved complete response (CR), 16 (14.5%) achieved partial response (PR) and 40 (36.4%) achieved stable disease (SD) lasting longer than 8 weeks. The median OS and PFS for the whole cohort were 10.5 [95% confidence interval (CI), 8.7-12.3] and 5.0 months (95% CI, 3.7-6.3), respectively. Sorafenib in combination with local therapy was an independent predictor for longer PFS, whereas Eastern Cooperative Group (ECOG) performance status (PS) and Child-Pugh class were associated with reduced PFS. Local therapy was associated with longer OS while ECOG PS and α-fetoprotein were associated with reduced OS. In a subset of patients with radiological progressive disease, a significant difference was found in OS between patients who continued taking sorafenib and those who discontinued therapy (11 vs. 7.5 months, P<0.001). In conclusion, sorafenib in combination with local therapy (transarterial chemoembolization with/without cryoablation) was independently associated with longer OS and PFS in advanced HCC patients. Poor ECOG PS was associated with shorter OS and PFS and is thus a marker of poor outcomes in sorafenib-treated HCC patients.

Overexpression of metastasis-associated in colon cancer 1 predicts a poor outcome of hepatitis B virus-related hepatocellular carcinoma.

AIM: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed. RESULTS: Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival (TFS) and overall survival (OS) were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels (TFS: 34 mo vs 48.0 mo, P < 0.001; OS: 40 mo vs 48 mo, P < 0.01). Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome (P < 0.001). CONCLUSION: High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.

[Expression and clinical significance of metastasis-associated in colon cancer 1 (MACC1) in HBV-related hepatocellular carcinoma].

OBJECTIVE: To clarify the expression and clinical significance of metastasis-associated in colon cancer 1 (MACC1) mRNA in hepatocellular carcinoma (HCC). METHODS: The expression and distribution of MACC1 were assessed by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining (IHC) in a cohort of hepatitis B virus-related HCC, including 138 in early (A), 96 in intermediate (B) and 120 in advanced stages (C). The association of MACC1 mRNA with disease progression and outcomes was analyzed by univariate and multivariate Cox analysis. RESULTS: The intratumoral expressions of MACC1 mRNA in HCC stage I (0.001 76, range: 0.000 54 - 0.002 47), stage II (0.002 49, range: 0.000 55 - 0.006 78) and stage III (0.008 35, range: 0.006 86 - 0.009 88) were about 3-, 4- and 14-fold higher than that in the normal liver tissue (0.000 59, range: 0.000 57 - 0.000 60), respectively. Intratumoral expression of MACC1 mRNA increased with disease progression from stage I to stage III. HCC clinical staging classification, age, portal vein invasion and tumor differentiation were significantly associated with intratumoral high expression of MACC1 mRNA (All P < 0.05). Immunohistochemical staining showed that there was an increased MACC1 expression in cytoplasm of HCC cells and positive nuclear staining in some cases. Increased MACC1 mRNA expression could predict poor outcome and recurrence in stage A and B HCC postoperatively. The median tumor-free survival and total survival of patients with high MACC1 mRNA expression were 34.0 and 40 months, respectively, significantly lower than that in those with low expression (48.0 and 48.0 months) (all P < 0.01). Cox analysis showed that Child-Pugh grading and high expression of MACC1 mRNA were independent predictive factors, and high expression of MACC1 was an independent predictive factor affecting the tumor-free survival. CONCLUSIONS: MACC1 mRNA up-regulation is a feature of disease progression in HCC. MACC1 mRNA expression in the HCC may become an independent predictive factor for recurrence and survival in postoperative HCC patients.